The present invention relates generally to intravascular radiotherapy, and more particularly to improved devices and methods for delivering nuclear radiation therapy to avoid restenosis in blood vessels that have been subjected to an interventional dilatation procedure.
U.S. Pat. No. 5,199,939 to Dake et al. discloses a technique for inhibiting restenosis in a coronary artery following angioplasty by delivering nuclear radiation therapy to the artery wall at the time or immediately after the angioplasty procedure is performed.
In co-pending patent applications Ser. Nos. 08/057,322, 08/339,950 and 08/467,711 of A. J. Bradshaw et al., which are assigned to a common assignee, and incorporated herein by reference in their entirety, devices and techniques are disclosed for improved delivery of intravascular radiotherapy by substantially centering the radioactive source in the tortuous pathway of a coronary artery to provide a relatively uniform dose of radiation to preselected tissue of the arterial wall at the target site in a substantially circumferential band disposed a predetermined radial distance from the radioactive source. It is essential that a uniform dose of radiation be delivered to the preselected tissue in the designated circumferential band about the source, rather than a random or non-uniform dose. Otherwise, tissue segments at locations on the interior surface of the wall closer to and further from the source would be overdosed and underdosed, respectively. Overdosing is to be avoided because it causes excessive vessel hemorrhaging, excessive fibrous media thinning, and the possibility of aneurysm or other late radiation effects. J. Weinberger et al. of Columbia University have suggested in a published study that overdosing also may be slightly stimulative in some dose ranges. Underdosing should also be avoided because it does not inhibit the proliferative cellular growth which is a traumatic response to the initial interventional dilatation, and hence, does not substantially deter restenosis.
In a clinical setting, it is desirable to administer the intravascular radiotherapy in as short a time as is practicable, to avoid the blood flow reduction and other factors which can lead to adverse consequences from leaving the catheter and radioactive source (so-called source wire) in place in the coronary artery or other portion of the vasculature for too long a time. Treatment time may be shortened by increasing the activity level of the radioactive source.
Studies by the Frankfort Group and Emory University have indicated that very high activity radioactivity sources stepped through the target site with relatively short treatment times, i.e., where the source is of shorter length than the length of arterial wall which is to be treated and must therefore be incrementally advanced (or retracted)--or "stepped"--through the target site during treatment, have yielded mixed results. Neither of these cited studies used techniques to assure centering of the radioactive source, and each used a standard oncology catheter in delivery of the radiation. Research conducted by the applicants herein using a high activity stepping source without centering to treat coronary arteries in pigs yielded mixed results, with the relatively straight circumflex (CFX) and left anterior descending (LAD) arteries exhibiting a dose response with 1000 rads (r, or centiGray, cGy) which is similar to the control arteries. A better response was achieved with 1500 r, and even better with 2500 r. In that regard, the term "better" is used as reflecting improved results in percentage of area stenosis, in maximal intimal thickness, and in mean luminal area, compared to control. The right coronary artery (RCA) results showed no dose response and no improvement at any of the three doses, thought by the applicants to be attributable to lack of dose control in this severely curved artery because no centering mechanism was used to preclude random overdosing and underdosing.
Further testing and data analysis by the applicants has suggested another mechanism responsible for the poor RCA results and the mixed results encountered in other high activity studies. It is a primary objective of the present invention to provide improvements in the methods and apparatus for inhibiting restenosis in blood vessels subjected to angioplasty procedures.